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ZAP-Gene: Charakterisierung der Proteinstruktur einer neuen Familie proliferationsassoziierter Gene im exokrinen Pankreas

ZAP genes: Characterizing the protein structure of a new family of proliferation-associated genes in exocrine pancreas

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Zusammenfassung

□ Bei Untersuchungen zur wachstumsabhängigen Genregulation konnten wir aus einer Pankreaskarzinomzellinie eine Gruppe Zinkfingermotive, Ankyrindomänen und Pleckstrinhomologien enthaltender Proteine (ZAP) klonieren. Beispiele der funktionellen Bedeutung dieser Domänen finden sich in Proteinen, die an verschiedenen Signaltransduktionskaskaden und der Regulation des Zellzyklus beteiligt sind. Weiterhin konnten für die einzelnen ZAP-Proteine spezifische Funktionsmotive, ihre chromosomale Lokalisation und gewebespezifische Transkription charakterisiert werden. Die bisher ermittelten Daten deuten auf ein breites Spektrum potentieller Protein-Protein-Interaktionen hin. Spezifische Interaktionspartner sind zum jetzigen Zeitpunkt noch nicht identifiziert.

□ Zusammenfassend könnte es sich aufgrund der Vielzahl von sehr gut definierten Proteindomänen und der transkriptionellen Daten bei den Mitgliedem der ZAP-Familie um Scaffold-Proteine im komplexen Netzwerk wachstums-assoziierter intrazellulärer Signaltransduktionskaskaden handeln.

Abstract

□ While interested in proliferation-dependent gene regulation in a pancreatic carcinoma cell line, we cloned a set of proteins (ZAP) characterized by a conserved region consisting of consecutive zinc finger, ankyrin repeat and PH domains. Functional aspects of these domains were obtained by comparison with proteins involved in several signal transduction pathways and cell cycle regulation. The members of the ZAP protein family are individually characterized by different types of supplementary protein family are individually characterized by different types of supplementary protein domains, their chromosomal localization and their tissue specific gene transcription. All results indicate a wide spectrum of protein-protein interactions. Up to now specific binding partners have not been identified.

□ In summary, the multiplicity of conserved regions and transcriptional data indicate a scaffold function for ZAP proteins in the complex network of proliferation associated intracellular signal transduction pathways.

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Literatur

  1. Bauer D, Müller H, Reich J, et al. Identification of differentially expressed mRNA species by an improved display technique (DDRT-PCR). Nucleic Acids Res 1993: 21: 4272–80.

    Article  PubMed  CAS  Google Scholar 

  2. Bellacosa A, Chan TO, Ahmed NN, et al. Akt activation by growth factors is a multiple-step process: the role of the PH-domain. Oncogene 1998; 17: 313–5.

    Article  PubMed  CAS  Google Scholar 

  3. Bennet V. Ankyrins. J Biol Chem 1992; 267: 8703–6.

    Google Scholar 

  4. Blank V, Kourilsky P, Israel A. NF-kB and related proteins: Rel/dorsal homologies meet ankyrin-like repeats. TIBS 1992; 17: 135–40.

    PubMed  CAS  Google Scholar 

  5. Fearon BR, Vogelstein B. A genetic model for colorectal tumorgenesis. Cell 1990; 61: 759–67.

    Article  PubMed  CAS  Google Scholar 

  6. Galcheva Gargova Z, Konstantinov KN, Wu IH, et al. Binding of zinc finger protein ZPR1 to the epidermal growth factor receptor. Science 1996; 272: 1797–1802.

    Article  PubMed  CAS  Google Scholar 

  7. Gorina S, Pavletich NP. Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2. Science 1996; 274: 1001–5.

    Article  PubMed  CAS  Google Scholar 

  8. Gress TM, Lutz MP, Adler G. Aktuelle Aspekte in der Diagnostik und Therapie des Pankreaskarzinoms. Z Gastroenterol 1997; 35: Suppl 1: 11–41.

    Google Scholar 

  9. Haslam RJ, Koide HB, Hennings BA. Pleckstrin domain homology. Nature 1993; 363: 309–10.

    Article  PubMed  CAS  Google Scholar 

  10. Hemmings BA. PH-Domains—an universal membrane adapter. Science 1997; 275: 1899–1900.

    Article  PubMed  CAS  Google Scholar 

  11. Hilgers W, Schmiegel W. neue Aspekte in der Pathogenese des Pankreaskarzinoms. Z. Gastroenterol 1997; 35: Suppl 1: 4–10.

    Google Scholar 

  12. Hopkin K. A surprising function for the PTEN tumor suppressor. Science 1998; 282: 1027–30.

    Article  PubMed  CAS  Google Scholar 

  13. Hyvönen M, Saraste M. Structure of the PH domain and Btk motif from Bruton’s tyrosin kinase: molecular explanations for X-linked agammaglobulinaemia. EMBO J 1997; 16: 3396–3404.

    Article  PubMed  Google Scholar 

  14. Klug A, Schwabe JWR. Zinc fingers. FASEB J 1995; 9: 597–604.

    PubMed  CAS  Google Scholar 

  15. Luo Z, Dias B, Marshall MS, Avruch J. An intact Raf zinc finger is required for optimal binding to processed Ras and for ras-dependent Raf activation in situ. Mol Cell Biol 1997; 17: 46–53.

    PubMed  CAS  Google Scholar 

  16. MacKay JP, Crossley M. Zinc fingers are sticking together. TIBS 1998; 23: 1–4.

    PubMed  CAS  Google Scholar 

  17. Moskaluk CA, Hruban RH, Kern SE. p16 and K-ras gene mutation in the intraductal precursors of human pancreatic adenocarcinomas. Cancer Res 1997; 57: 2140–3.

    PubMed  CAS  Google Scholar 

  18. Nomura N, Nagase T, Miyajima N, et al. Prediction of the coding sequences of unidentified human genes. DNA Res 1994; 1: 223–9.

    Article  PubMed  CAS  Google Scholar 

  19. Russo AA, Tong L, Lee JO, Jeffrey PD, Pavletich NP. Structural basis for inhibition of the cyclin-dependnet kinase Cdk6 by the tumor suppressor p16INK4a. Nature 1998; 395: 237–43.

    Article  PubMed  CAS  Google Scholar 

  20. Sachdev S, Hoffmann A, Hannink M. Nuclear localization of IκBα is mediated by the second ankyrin repeat: the IκBα ankyrin repeats define a novel class of cis-acting nuclear import sequences. Mol Cell Biol 1988; 18: 2524–34.

    Google Scholar 

  21. Tyers M, Rachubinski RA, Stewart MI et al. Molecular cloning and expression of the major protein kinase C substrate of platelets. Nature 1988; 333: 470–3.

    Article  PubMed  CAS  Google Scholar 

  22. Wetzker R. Phosphoinositid-3-Kinasen im Netzwerk der intrazellulären Signalübertragung. Biospektrum 1998; 4: 35–8.

    CAS  Google Scholar 

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Correspondence to Rainer Günther.

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Günther, R., Zill, H., Schmidt, W.E. et al. ZAP-Gene: Charakterisierung der Proteinstruktur einer neuen Familie proliferationsassoziierter Gene im exokrinen Pankreas. Med Klin 94, 233–238 (1999). https://doi.org/10.1007/BF03044861

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